ADAMs Answer To Heart Failure

In cases of increased blood pressure, the heart has to pump extra hard to circulate blood around the body. Because the heart is a muscle, over a period of time this extra exertion causes the muscle to grow larger - a phenomenon known as cardiac hypertrophy. Paradoxically, although the heart, namely the left ventricle, is larger, it is less effective and heart disease ensues. Thus, curing cardiac hypertrophy is a medical goal.

Scientists at Osaka University Faculty of Medicine in Japan have discovered a set of molecular events that may underlie cardiac hypertrophy and prove to be a target for drug intervention (Nature Medicine, Vol. 8, No. 1, p. 35, 01 Jan 02).

Shigeki Higashiyama and colleagues discovered that under increased pressure, a member of the ADAMs family of proteins, ADAM12, cleaves another molecule called HB-EGF that liberates EGF which is then able to go on and stimulate the growth of the heart muscle. Agents that block the action of ADAM12, such as KB-R7785, may therefore be useful in hypertrophy.

In an accompanying News & Views article (p. 20), James Liao of Brigham & Women's Hospital, Massachusetts points out the caveats of the findings. For example, he points out that other molecular pathways may compensate for the one put out of action by an ADAM12 inhibitor, and hypertrophy may occur even with this type of treatment.